A simple and robust method to measure anisotropic arterial wall viscoelasticity would help with our understanding of disease progression. Also, it can assist with developing new drug regimens addressing new targets in the arterial wall. Estimation of the material properties of the arterial wall is a very complex problem because of the complexity of the wall itself. To approach this problem, we have designed a four-component program of investigation. The first part, described in Specific Aim 1, is designed to complete the mathematical and computational foundations that will support our newly developed methods of estimating anisotropic and viscoelastic material properties from measurable arterial wall responses to applied radiation force. This part of the investigation covers computation of the radiation stress from the ultrasound beams and two approaches to solving the inverse problem e.g., an analytic computational inverse method and an iterative FEM inverse method. The second part of the program, Aim 2, is designed to give laboratory based validation of the methods developed in Aim 1. The validation will be conducted on excised arteries and tubes. In addition, the dependence of the material properties on various constituents of the artery such as elastin and collagen will be determined. This Aim goes hand in hand with the third component, Aim 3, implementation of the developed methods in live pigs. The point is to test the methods in pig arteries that have a wide range of stiffness induced by disease, in this case, induced hypertension. Histomorphometry will be done on the arteries of the pigs and correlated with the measured viscoelastic moduli of the arterial walls. To begin the clinical application of these methods, in Aim 4, measurements will be made of the anisotropic viscoelastic moduli of arteries in humans that are already enrolled in ongoing clinical studies. Classical arterial stiffness measurements such as PWV and augmentation index, and pulse pressure, will be correlated to the viscoelastic arterial wall moduli measured with the new system. Implementation in a clinical scanner of the methods developed here will allow us to make measurements in humans using a portable scanner that can be added to NIH funded clinical trials with minimal modification of the ongoing protocols and minimal cost. Successful completion of these studies will result in knowledge of the relationship of the viscoelastic arterial wall moduli to an array of clinical attributes in the studied populations resulting in a valuable clinical ultrasound tool. PUBLIC HEALTH RELEVANCE: The long-term goal of this program is to noninvasively measure arterial wall material properties with high accuracy and precision using our novel vibrometry methods. The resulting quantitative measures will be amenable to clinical applications and population studies. The advantages of the methods proposed here are that they are noninvasive and fast allowing real-time measurement of arterial properties; they do not need estimates of transmural pressure; and they take into account the fact that properties are a function of frequency and direction within the arterial wall. Successful completion of this program will result in a new noninvasive scientific and clinical tool for measuring the viscoelastic frequency dependent anisotropic shear moduli of the vessel wall with higher temporal and spatial resolution than currently available.